RESUMO
We examined achromatic contrast discrimination in asymptomatic carriers of 11778 Leber's hereditary optic neuropathy (LHON 18 controls) and 18 age-match were also tested. To evaluate magnocellular (MC) and Parvocellular (PC) contrast discrimination, we used a version of Pokorny and Smith's (1997) pulsed/steady-pedestal paradigms (PPP/SPP) thought to be detected via PC and MC pathways, respectively. A luminance pedestal (four 1 degree x 1 degree squares) was presented on a 12 cd/m2 surround. The luminance of one of the squares (trial square, TS) was randomly incremented for either 17 or 133 ms. Observers had to detect the TS, in a forced-choice task, at each duration, for three pedestal levels: 7, 12, 19 cd/m2. In the SPP, the pedestal was fixed, and the TS was modulated. For the PPP, all four pedestal squares pulsed for 17 or 133 ms, and the TS was simultaneously incremented or decremented. We found that contrast discrimination thresholds of LHON carriers were significantly higher than controls' in the condition with the highest luminance of both paradigms, implying impaired contrast processing with no evidence of differential sensitivity losses between the two systems. Carriers' thresholds manifested significantly longer temporal integration than controls in the SPP, consistent with slowed MC responses. The SPP and PPP paradigms can identify contrast and temporal processing deficits in asymptomatic LHON carriers, and thus provide an additional tool for early detection and characterization of the disease.
Assuntos
Sensibilidades de Contraste , Triagem de Portadores Genéticos , Atrofia Óptica Hereditária de Leber/genética , Adolescente , Adulto , Discriminação Psicológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Testes Visuais , Acuidade Visual , Vias VisuaisRESUMO
AIMS: To determine if asymptomatic carriers from a previously identified large pedigree of the Leber's hereditary optic neuropathy (LHON) 11778 mtDNA mutation have colour vision deficits. METHODS: As part of a comprehensive analysis of over 200 members of a large Brazilian LHON pedigree spanning seven generations, colour vision tests were obtained from 91 members. Colour vision was tested one eye at a time using the Farnsworth-Munsell 100 (FM-100) hue colour vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight colour temperature of 6700 kelvin, and neutral uniform background. Tests were scored using the FM-100 MS-Excel computer scoring program. Defects were determined and categorised as tritan, deutan, or protan. Categorisation of each dyschromatopsia was based on review of demonstrated axis computer generated plots and age adjusted error scores which coincided with Verriest 95% confidence intervals. Only the axis with the greatest magnitude error score was used to classify the defect. 55 of the 91 test subjects were LHON mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The remaining 36 subjects were age matched non-blood relatives (off pedigree), who served as controls. RESULTS: 27 of 55 carriers (49.10%) were shown to have colour vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. Nine of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. Six of these were deutan, and the remaining three were tritan dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The remaining one was a tritan defect. The difference between the two groups using a chi(2) test with one degree of freedom was statistically significant with a p value less that 0.001. CONCLUSIONS: Until now, LHON has always been characterised by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected by colour vision defects and may manifest other subtle, yet chronic, changes.
Assuntos
Defeitos da Visão Cromática/genética , DNA Mitocondrial/genética , Atrofia Óptica Hereditária de Leber/genética , Brasil , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Triagem de Portadores Genéticos , Humanos , Mutação , LinhagemRESUMO
We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del Río province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50% of samples and high formate concentration levels in almost 25% of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.
Assuntos
Surtos de Doenças , Deficiência de Ácido Fólico/complicações , Ácido Fólico/sangue , Ácido Fólico/líquido cefalorraquidiano , Formiatos/sangue , Formiatos/líquido cefalorraquidiano , Doenças do Nervo Óptico/epidemiologia , Consumo de Bebidas Alcoólicas , Feminino , Humanos , Masculino , Metanol/efeitos adversos , Pessoa de Meia-Idade , Doenças do Nervo Óptico/sangue , Doenças do Nervo Óptico/líquido cefalorraquidiano , Doenças do Nervo Óptico/induzido quimicamente , Fatores de Risco , Solventes/efeitos adversosRESUMO
We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del RÝo province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50 of samples and high formate concentration levels in almost 25 of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ácido Fólico/sangue , Ácido Fólico/líquido cefalorraquidiano , Deficiência de Ácido Fólico/complicações , Surtos de Doenças , Doenças do Nervo Óptico/epidemiologia , Formiatos , Consumo de Bebidas Alcoólicas , Doenças do Nervo Óptico/sangue , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Nervo Óptico/líquido cefalorraquidiano , Metanol , Fatores de Risco , SolventesRESUMO
OBJECTIVE: To search for mitochondrial DNA (mtDNA) mutations previously associated with Leber's hereditary optic neuropathy (LHON) in patients with an optic neuropathy that appeared in epidemic form in Cuba. METHODS: Twelve Cuban patients underwent a comprehensive neuro-ophthalmologic examination and were found to have a characteristic optic neuropathy, Cuban epidemic optic neuropathy (CEON). At the same time, one patient was diagnosed with typical LHON that occurred during the epidemic. Blood samples were taken from these patients as well as from 3 controls with normal neuro-ophthalmologic examinations. These samples were blindly analyzed for 9 LHON-associated mtDNA mutations by molecular genetic methods. RESULTS: CEON bore clinical and epidemiological similarity to LHON, however, family histories, systemic symptoms (especially weight loss and polyuria), and symptoms of peripheral neuropathy permitted a clinical distinction. None of the 12 patients with CEON or 3 controls had any of the LHON-associated mtDNA mutations. Only the patient with clinical LHON, who did not meet the case definition for CEON, harbored the 11778 mtDNA mutation. CONCLUSIONS: Known mtDNA mutations are not found frequently in CEON patients but they may contribute to some cases of Cuban optic neuropathy. CEON may represent an acquired variety of mitochondrial dysfunction induced by nutritional deficiencies, toxins, or both. Alternatively, CEON patients may also harbor as yet undiscovered mtDNA mutations that contribute to their genetic susceptibility.
Assuntos
DNA Mitocondrial , Atrofias Ópticas Hereditárias/genética , Doenças do Nervo Óptico/epidemiologia , Doenças do Nervo Óptico/genética , Cuba/epidemiologia , Análise Mutacional de DNA , Surtos de Doenças , Feminino , Humanos , Masculino , Mutação , Atrofias Ópticas Hereditárias/epidemiologia , Atrofias Ópticas Hereditárias/etiologia , Doenças do Nervo Óptico/etiologia , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
OBJECTIVE: To characterize and establish a clinical definition of the optic neuropathy that appeared in epidemic form in Cuba in 1992 and 1993. METHODS: At the invitation of the Cuban Ministry of Health, Havana, members of ORBIS International and the Pan American Health Organization, assembled teams that traveled to Cuba in May 1993. We were initially briefed by Cuban national experts in the areas of virology, nutrition, toxicology, ophthalmology, neurology, and public health. We then examined 20 patients on our own. Thirteen of these patients underwent a comprehensive neuro-ophthalmologic examination, including neurologic examination, ophthalmologic examination, visual fields, optic nerve function studies, contrast sensitivity studies, and funduscopy. We returned 4 months later to perform an additional 12 comprehensive neuro-ophthalmologic and follow-up examinations. RESULTS: Only seven of the 13 patients who were alleged to have the optic form of the epidemic and who were rigorously and systematically examined on the first visit demonstrated a bilateral optic neuropathy. These seven patients had several features that included decreased visual acuity, poor color vision, central scotomas, decreased contrast sensitivity, saccadic eye movements, and most prominent and distinctive of all, nerve fiber layer wedge defects of the papillomacular bundle. Our clinical definition was then implemented by the Cuban ophthalmologists and epidemiologists. On returning 4 months later, we found that all newly presented patients were correctly diagnosed to have the epidemic disease. With the new case definition and the application of a few simple psychophysical tests, the false-positive rate of diagnosis became much lower. After vitamin therapy, we reexamined the patients seen on our initial visit, and all showed marked improvement. CONCLUSIONS: The Cuban epidemic was characterized by an optic neuropathy with features that were similar to those of tobacco/alcohol amblyopia and Leber's optic atrophy. Recent political, economic, and social changes in Cuba may have contributed to the nutritional and/or toxic compromise of mitochondrial function of an acquired nature, which led to selective retinal ganglion cell damage. We have termed this condition Cuban epidemic optic neuropathy.
Assuntos
Surtos de Doenças , Fundo de Olho , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/epidemiologia , Adulto , Cuba/epidemiologia , Feminino , Humanos , Incidência , Masculino , Doenças do Nervo Óptico/terapiaRESUMO
We made two trips to Cuba, as part of an invited international delegation, to investigate an epidemic of optic neuropathy-induced blindness. We worked closely with Cuban scientists and clinicians in their efforts to understand and then deal with 50,000 cases of blindness and an entire population at risk. This gave an unparalleled opportunity to understand the Cuban system of ophthalmologic health care and, in particular, to appreciate the responses of the scientific and health care communities to this crisis. Several features of the very different Cuban medical and scientific infrastructure were both problematic and advantageous as they affected the Cuban efforts to understand, contain and treat this remarkable epidemic.